DESCRIPTION: The long-term objectives of this project are to understand how steroid hormones evoke diverse patterns of differentiation in the nervous system. Combined studies on Drosophila and Manduca provide a wide range of genetic and endocrine approaches for studying the action of the steroid hormones, the ecdysteroids. These steroids are normally released during a major surge that may last for days. The chemical nature of the steroids that are present change during the surge as does the character of the tissue response and the isoform of ecdysone receptor (EcR) that is present. These studies focus on several neural systems to examine the relationship between types of steroids, receptor isoforms and neuronal responses. The assessment of neuronal response is in terms of the expression of a set of ecdysone-responsive genes that comprise a transcription factor cascade which presumably orchestrates the tissue's response to steroid. The nature of this response can also be regulated by a second hormone, the juvenile hormone. Specific aims are to: 1) Characterize the expression pattern of representatives of the ecdysone-responsive genes in both Manduca and Drosophila to determine the relationship of their expression to the steroid titers and to EcR isoforms. 2) Perform a mosaic analysis in tissue patches which lack EcR isoforms or its heterodimeric partner, ultraspiracle (USP), to determine roles of particular isoforms in directing the steroid response. 3) Use hormonal manipulation of cultured nervous systems to determine the role of the various ecdysteroids in controlling EcR isoform expression and in the expression pattern of ecdysone responsive genes. 4) Use juvenile hormone treatments to try to redirect EcR expression and to modify the pattern of ecdysone responsive gene expression. The latter will then be related to the effects of such treatments on neuronal responses.